3hq5: Difference between revisions

Revision as of 07:44, 1 November 2017

Progesterone Receptor bound to an Alkylpyrrolidine ligand.

Structural highlights

3hq5 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	GKK, GOL, SO4
Gene:	PGR, NR3C3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PRGR_HUMAN] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists.,Thompson SK, Washburn DG, Frazee JS, Madauss KP, Hoang TH, Lapinski L, Grygielko ET, Glace LE, Trizna W, Williams SP, Duraiswami C, Bray JD, Laping NJ Bioorg Med Chem Lett. 2009 Aug 15;19(16):4777-80. Epub 2009 Jun 17. PMID:19595590^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
↑ Thompson SK, Washburn DG, Frazee JS, Madauss KP, Hoang TH, Lapinski L, Grygielko ET, Glace LE, Trizna W, Williams SP, Duraiswami C, Bray JD, Laping NJ. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4777-80. Epub 2009 Jun 17. PMID:19595590 doi:10.1016/j.bmcl.2009.06.055

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OCA

[1] Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004

[2] Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885

[3] Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691

[4] Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602

[5] Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248

[6] Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X

[7] Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437

[8] Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004

[9] Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885

[10] Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691

[11] Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602

[12] Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248

[13] Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X

[14] Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437

[15] Thompson SK, Washburn DG, Frazee JS, Madauss KP, Hoang TH, Lapinski L, Grygielko ET, Glace LE, Trizna W, Williams SP, Duraiswami C, Bray JD, Laping NJ. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4777-80. Epub 2009 Jun 17. PMID:19595590 doi:10.1016/j.bmcl.2009.06.055

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@@ Line 1: / Line 1: @@
 ==Progesterone Receptor bound to an Alkylpyrrolidine ligand.==
 <StructureSection load='3hq5' size='340' side='right' caption='[[3hq5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GKK:2-CHLORO-4-{[(3S)-1-METHYLPYRROLIDIN-3-YL][2-(TRIFLUOROMETHYL)BENZYL]AMINO}BENZONITRILE'>GKK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGR, NR3C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hq5 OCA], [http://pdbe.org/3hq5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hq5 RCSB], [http://www.ebi.ac.uk/pdbsum/3hq5 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hq5 OCA], [http://pdbe.org/3hq5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hq5 RCSB], [http://www.ebi.ac.uk/pdbsum/3hq5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hq5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 3hq5" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Hormone|Hormone]]
 == References ==
 <references/>
@@ Line 39: / Line 37: @@
 [[Category: Washburn, D G]]
 [[Category: Williams, S P]]
+[[Category: Alternative splicing]]
+[[Category: Cytoplasm]]
 [[Category: Dna-binding]]
 [[Category: Hormone binding protein]]
@@ Line 47: / Line 47: @@
 [[Category: Nucleus]]
 [[Category: Phosphoprotein]]
+[[Category: Polymorphism]]
 [[Category: Pr]]
 [[Category: Progesterone receptor]]
@@ Line 53: / Line 54: @@
 [[Category: Transcription]]
 [[Category: Transcription regulation]]
+[[Category: Ubl conjugation]]
+[[Category: Zinc]]
 [[Category: Zinc-finger]]

3hq5: Difference between revisions

Revision as of 07:44, 1 November 2017

Progesterone Receptor bound to an Alkylpyrrolidine ligand.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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